More effective agents against solid tumors are urgently needed, and chemically reactive compounds, which are expected to react covalently with cellular components under physiological conditions, are generally more effective against solid tumors than are antimetabolites. Our previous studies with nitrosoureas and triazenes, two classes of compounds that have furnished clinically active agents, indicate that haloethylating agents-compounds that introduce a haloethyl group into biological macromolecules-are exceptionally effective in manifesting antineoplastic activity. For these reasons, four types of structures that are expected to function as haloethylating agents have been selected for study. Three other classes of chemically reactive compounds are included in this research. Fragmentation compounds that release a carbonium-immonium ion would, if active, comprise a new type of anticancer agent. N-Acyloxyamides and related compounds are known to react in vivo with DNA, RNA, and proteins. The development of effective agents from this type of structure would also provide a new class of anticancer agents. Certain dialdehydes have antineoplastic activity. Further investigation of this class of compounds is designed to delineate structural requirements for activity and to improve activity. The objectives of this proposal are to synthesize compounds representative of these types of structures, evaluate these compounds for antineoplastic activity in vivo and in vitro, and investigate the biochemical mechanism of action of active agents.